Synthesis and biological evaluation of potent glycosidase inhibitors: 4-deoxy-4,4-difluoroisofagomine and analogues

A series of 4,4-difluoroisofagomine analogues were synthesized. These compounds were tested for inhibition of eight glycosidases. The 3 R,5 R isomer 1 is a new and potent inhibitor against β-glucosidase from almonds with K i value of 1.2 μM. The influence of the gem-difluoromethylene group (CF 2) on...

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Bibliographic Details
Published in:Tetrahedron 2009-05, Vol.65 (18), p.3717-3727
Main Authors: Li, Rui-jie, Bols, Mikael, Rousseau, Cyril, Zhang, Xin-gang, Wang, Ruo-wen, Qing, Feng-Ling
Format: Article
Language:English
Subjects:
Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides
Carbohydrates. Nucleosides and nucleotides
Chemistry
Exact sciences and technology
Fluorinated compounds
Glycosidases inhibitors
Heterocyclic compounds
Heterocyclic compounds with only one n hetero atom and condensed derivatives
Iminosugar
Organic chemistry
Preparations and properties
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Summary:A series of 4,4-difluoroisofagomine analogues were synthesized. These compounds were tested for inhibition of eight glycosidases. The 3 R,5 R isomer 1 is a new and potent inhibitor against β-glucosidase from almonds with K i value of 1.2 μM. The influence of the gem-difluoromethylene group (CF 2) on binding to glycosidases is discussed. It is concluded that only non-essential hydroxyl groups can be replaced by the gem-difluoro group and that in such a case (β-glycosidase) the change in inhibition is, interestingly, a result of the change in base strength. [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2009.02.079